Mice born with combined lipase deficiency develop severe hyperlipemia and die within 3 days if allowed to suckle. This condition is caused by a recessive mutation (cld) in the T/t complex of chromosome 17, and is characterized by marked functional deficiencies of both lipoprotein and hepatic lipases. We reported earlier that brown adipose tissue, heart and diaphragm muscle of cld/cld mice synthesize lipoprotein lipase that is normal in size, but the enzyme is inactive and retained in the tissues. Since lipoprotein lipase is a glycoprotein and mutations in the T/t complex of chromosome 17 can affect glycosylation of proteins, it seemed possible that defective glycosylation could account for lack of activity, and possibly lack of secretion, of lipoprotein lipase in cld/cld mice. We are now studying this possiblity in adipocytes cultured from brown adipose tissue. We found that cells cultured from both cld/cld and normal mice readily converted to adipocytes when grown in medium containing triiodothyronine, insulin and octanoic acid. However, only adipocytes from normal mice released active lipoprotein lipase to the medium. Preliminary studies, using fluorescent immunocytochemical techniques, showed that adipocytes from cld/cld mice contained intracellular lipoprotein lipase, whereas adipocytes from normal mice had lipase, in small amounts, only on cell surfaces. These findings show that cultured adipocytes from defective mice synthesize a non-secretable form of lipoprotein lipase, whereas those from normal mice synthesize and secrete active lipase. Thus, cultured adipocytes can be used to study in vitro the genetic and chemical nature of the lipoprotein lipase deficiency in cld/cld mice.